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Locally Advanced Breast Cancer: Individualized Treatment Based On Tumor Molecular Characteristics

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ClinicalTrials.gov Identifier: NCT02297230
Recruitment Status : Terminated (PI Left Institution prior to reaching accrual goal and analyzing data.)
First Posted : November 21, 2014
Results First Posted : January 18, 2018
Last Update Posted : October 15, 2018
Sponsor:
Information provided by (Responsible Party):
NYU Langone Health

Brief Summary:

Paclitaxel 30 mg/m2 twice/week Trastuzumab 4mg/kg, loading dose, then 2 mg/kg weekly and Concurrent RT (to start within one week from first dose of Paclitaxel/Trastuzumab) to breast, supraclavicular, axillary fields, 45 Gy @ 1.8 Gy/fraction, + 14 Gy @ 2 Gy/fraction to the primary tumor. At the end of chemo-radiation, Trastuzumab will be continued weekly until surgery and as per standard of care after surgery for up to 1 year total.

**Surgery: Patients will undergo lumpectomy and axillary node dissection or modified radical mastectomy within two months following discontinuation of pre-operative systemic therapy, contingent upon recovery of skin toxicity. Pathologic response will be evaluated at the time of surgery. Additional tissue samples will be collected from the surgical specimen for assessment of tumor molecular characteristics.

***All patients may undergo four cycles of post-operative Standard AC (doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2) or four cycles of post-operative epirubicin and Cyclophosphamide (epirubicin 100 mg/m2, cyclophosphamide 600 mg/m2) if doxorubicin is not available Tamoxifen as well or any alternative antihormonal therapy may be prescribed for five years for patients with hormone receptor positive tumors. Herceptin (Trastuzumab) will be prescribed for a total of 1 year since first dose as per standard of care.


Condition or disease Intervention/treatment Phase
Breast Cancer Radiation: Radiation Therapy (RT) Drug: Capecitabine Drug: Trastuzumab Drug: Paclitaxel Phase 1 Phase 2

Detailed Description:
Locally Advanced Breast Cancer: T greater than 3.0 cm. HER-2/neu positive. Patients with ipsilateral supraclavicular nodes are eligible. Patients with inflammatory breast cancer or distant metastases are excluded. Patients with prior treatment for their breast cancer are excluded. Patients must have adequate laboratory parameters and normal cardiac function. Patients receive Concurrent Radiation therapy with either Capecitabine, Paclitaxel and Herceptin. Capecitabine (Xeloda®) 750 mg/m2 twice/daily given orally. Treatment should begin on day 1 of radiation therapy. The two doses should be taken about 30 minutes after eating (eg. after breakfast and after dinner). Treatment will be given for 10 weeks (for 6 weeks during radiation and for 4 weeks after radiation).Trastuzumab (Herceptin®) will begin on day 1 of radiation therapy and be administered weekly. The first dose will be 4mg/kg given IV over 90 minutes. Subsequent weekly doses will be 2 mg/kg/week IV over 30 minutes. Paclitaxel 30 mg/m2 twice per week given IV over 1 hour. Treatment will be initiated during the first week of radiation therapy and should be administered on a Monday/Thursday or Tuesday/Friday schedule.Paclitaxel 30 mg/m2 twice per week given IV over 1 hour. Treatment will be initiated during the first week of radiation therapy and should be administered on a Monday/Thursday or Tuesday/Friday schedule.Trastuzumab (Herceptin®) treatment will be administered weekly, together with one of the two weekly doses of Paclitaxel. The first dose will be 4mg/kg given IV over 90 minutes. Subsequent weekly doses will be given at a dose of 2 mg/kg/week IV over 30 minutes. The treatment with Trastuzumab will continue weekly after the completion of the radiation treatment until surgery and thereafter as per standard of care up to 1 year post surgery.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Locally Advanced Breast Cancer: Individualized Treatment Based On Tumor Molecular Characteristics
Study Start Date : June 2002
Actual Primary Completion Date : December 2, 2014
Actual Study Completion Date : December 2, 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Paclitaxel

Arm Intervention/treatment
Experimental: Arm 1 Capecitabine and RT
Her-2/neu negative patients will be given Capecitabine (xeloda, 750mg/m2 twice daily orally. Treatment should begin on day 1 of radiation therapy. The two doses should be taken about 30 minutes after eating (eg. after breakfast and after dinner). Treatment will be given for 10 weeks (for 6 weeks during radiation and for 4 weeks after radiation).
Radiation: Radiation Therapy (RT)
Concurrent RT (to start within one week from first dose of Paclitaxel/Trastuzumab) to breast, supraclavicular, axillary fields, 45 Gy @ 1.8 Gy/fraction, + 14 Gy @ 2 Gy/fraction to the primary tumor. At the end of chemo-radiation, Trastuzumab will be continued weekly until surgery and as per standard of care after surgery for up to 1 year total.

Drug: Capecitabine
Capecitabine (Xeloda®) 750 mg/m2 twice/daily given orally. Treatment should begin on day 1 of radiation therapy. The two doses should be taken about 30 minutes after eating (eg. after breakfast and after dinner). Treatment will be given for 10 weeks (for 6 weeks during radiation and for 4 weeks after radiation).
Other Name: Xeloda

Experimental: Arm 2 Paclitaxel/Trastuzumab and RT
Trastuzumab (Herceptin®) will begin on day 1 of radiation therapy and be administered weekly to Her-2/neu Positive patients. The first dose will be 4mg/kg given IV over 90 minutes. Weekly doses will be 2 mg/kg/week IV over 30 minutes.Paclitaxel 30 mg/m2 twice per week given IV over 1 hour.
Radiation: Radiation Therapy (RT)
Concurrent RT (to start within one week from first dose of Paclitaxel/Trastuzumab) to breast, supraclavicular, axillary fields, 45 Gy @ 1.8 Gy/fraction, + 14 Gy @ 2 Gy/fraction to the primary tumor. At the end of chemo-radiation, Trastuzumab will be continued weekly until surgery and as per standard of care after surgery for up to 1 year total.

Drug: Trastuzumab
Trastuzumab (Herceptin®) treatment will be administered weekly, together with one of the two weekly doses of Paclitaxel. The first dose will be 4mg/kg given IV over 90 minutes. Subsequent weekly doses will be given at a dose of 2 mg/kg/week IV over 30 minutes. The treatment with Trastuzumab will continue weekly after the completion of the radiation treatment until surgery and thereafter as per standard of care up to 1 year post surgery.
Other Name: Herceptin

Drug: Paclitaxel
Paclitaxel 30 mg/m2 twice per week given IV over 1 hour. Treatment will be administered on a Monday/Thursday or Tuesday/Friday schedule.The radiation treatment will start within 1 week from the first dose of paclitaxel and trastuzumab. Pre-meds for paclitaxel should be based on the institutional standards; it is suggested that dexamethasone (Decadron®), 20 mg IV, be given with the first paclitaxel dose. If the patient tolerates the treatment, the dexamethasone may be tapered and/or discontinued for subsequent doses. Treatment will be given for 10 weeks (for 6 weeks during radiation and for 4 weeks following radiation).
Other Name: Taxol

Experimental: Arm 3: Paclitaxel and RT
Paclitaxel 30 mg/m2 twice per week given IV over 1 hour to Her-2/neu negative patients. Treatment will be initiated during the first week of radiation therapy and should be administered on a Monday/Thursday or Tuesday/Friday schedule.
Radiation: Radiation Therapy (RT)
Concurrent RT (to start within one week from first dose of Paclitaxel/Trastuzumab) to breast, supraclavicular, axillary fields, 45 Gy @ 1.8 Gy/fraction, + 14 Gy @ 2 Gy/fraction to the primary tumor. At the end of chemo-radiation, Trastuzumab will be continued weekly until surgery and as per standard of care after surgery for up to 1 year total.

Drug: Paclitaxel
Paclitaxel 30 mg/m2 twice per week given IV over 1 hour. Treatment will be administered on a Monday/Thursday or Tuesday/Friday schedule.The radiation treatment will start within 1 week from the first dose of paclitaxel and trastuzumab. Pre-meds for paclitaxel should be based on the institutional standards; it is suggested that dexamethasone (Decadron®), 20 mg IV, be given with the first paclitaxel dose. If the patient tolerates the treatment, the dexamethasone may be tapered and/or discontinued for subsequent doses. Treatment will be given for 10 weeks (for 6 weeks during radiation and for 4 weeks following radiation).
Other Name: Taxol

Experimental: Arm 4: Paclitaxel/Trastuzumab and RT
Trastuzumab (Herceptin®) tx will be administered weekly, together with one of the 2 weekly doses of Paclitaxel to Her-2/neu Positive patients. The 1st dose will be 4mg/kg given IV over 90 minutes. Weekly doses will b given at a dose of 2 17mg/kg/week IV over 30 minutes. The Tx with Trastuzumab will continue weekly after the completion of the radiation tx until surgery & thereafter as per std of care up to 1 yr post surgery.Paclitaxel 30 mg/m2 twice per week given IV over 1 hour. Tx will be administered on a Monday/Thursday or Tuesday/Friday schedule.The radiation treatment will start within 1 week from the first dose of paclitaxel and trastuzumab.
Radiation: Radiation Therapy (RT)
Concurrent RT (to start within one week from first dose of Paclitaxel/Trastuzumab) to breast, supraclavicular, axillary fields, 45 Gy @ 1.8 Gy/fraction, + 14 Gy @ 2 Gy/fraction to the primary tumor. At the end of chemo-radiation, Trastuzumab will be continued weekly until surgery and as per standard of care after surgery for up to 1 year total.

Drug: Trastuzumab
Trastuzumab (Herceptin®) treatment will be administered weekly, together with one of the two weekly doses of Paclitaxel. The first dose will be 4mg/kg given IV over 90 minutes. Subsequent weekly doses will be given at a dose of 2 mg/kg/week IV over 30 minutes. The treatment with Trastuzumab will continue weekly after the completion of the radiation treatment until surgery and thereafter as per standard of care up to 1 year post surgery.
Other Name: Herceptin

Drug: Paclitaxel
Paclitaxel 30 mg/m2 twice per week given IV over 1 hour. Treatment will be administered on a Monday/Thursday or Tuesday/Friday schedule.The radiation treatment will start within 1 week from the first dose of paclitaxel and trastuzumab. Pre-meds for paclitaxel should be based on the institutional standards; it is suggested that dexamethasone (Decadron®), 20 mg IV, be given with the first paclitaxel dose. If the patient tolerates the treatment, the dexamethasone may be tapered and/or discontinued for subsequent doses. Treatment will be given for 10 weeks (for 6 weeks during radiation and for 4 weeks following radiation).
Other Name: Taxol




Primary Outcome Measures :
  1. Feasibility & Efficacy of Chemo-radiation While Targeting Treatment, Based on: Original Tumor Characteristics; to be Followed by [Need for] Conventional Post-operative Chemotherapy [ Time Frame: 12/2014 (up to 12 years) ]

Secondary Outcome Measures :
  1. To Assess the Pathological Response Rate and Compare it to That Achieved in Our Previous Phase I-II Trials of Concurrent Chemo-radiation. [ Time Frame: 12/2014 (up to 12 years) ]
    No data displayed because Outcome Measure has zero total participants analyzed.

  2. To Store Core Biopsies of the Original Tumor Before and After Treatment (From the Surgical Specimen) for Future Molecular Biology Studies in LABC. [ Time Frame: 12/2014 (up to 12 years) ]
    No data displayed because Outcome Measure has zero total participants analyzed.

  3. To Acquire Descriptive Information on Patient Adherence to Therapy and on Quality of Life During Treatment. [ Time Frame: 12/2014 (up to 12 years) ]
    Data were not collected as PI left institution prior to enrollment completion. Planned Statistical analysis was not performed for this secondary outcome measure.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy proven locally advanced breast cancer: STAGE IIB (T must be > 3.0 cm, N0), IIIA (T0N2, T1N2, T2N2, T3N1), IIIB (T4N0-2).
  • HER-2/neu positive ( DAKO 3+ by Immunohistochemistry or FISH positive if Dako 2+)
  • Metastatic breast cancer: limited to the subset of patients with intact breast, locally advanced tumor and involved ipsilateral supraclavicular nodes.
  • Measurable disease required according to the RECIST criteria (Response Evaluation Criteria in Solid Tumors)
  • Adequate laboratory values:
  • Hgb > 10
  • ANC(Absolute Neutrophil Count) > 1500
  • Platelets > 150,000
  • Cr < 1.5
  • Liver function < 3 X normal.
  • Patient > 18 years of age.
  • Medically and psychologically able to comply with all study requirements.
  • ECOG (Eastern cooperative Oncology group) performance score 0-1.
  • Signed informed consent.

Exclusion Criteria:

  • Stage 0, Stage I, Stage IIA.
  • Previous XRT(Radiation therapy) or chemotherapy.
  • Presence of distant metastases documented clinically or radiographically with the exception of ipsilateral supraclavicular nodes.
  • Inflammatory breast cancer.
  • Prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil.
  • Exclude pregnant or lactating woman.
  • Woman of childbearing potential with either a positive or no pregnancy test at baseline.
  • Woman of childbearing potential not using a reliable and appropriate contraceptive method.
  • (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential).
  • Patient will agree to continue contraception for 30 days from the date of the last study drug administration.
  • Serious concurrent infections.
  • Clinically significant cardiac disease not well controlled with medication (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias ) or myocardial infarction within the last 12 months.
  • Patients who have had an organ allograft.
  • Patients with severe renal impairment (creatinine clearance below 30 mL/min [Cockcroft and Gault43]). In patients with moderate renal impairment (creatinine clearance 30-50 mL/min [Cockcroft and Gault43]) at baseline, a dose reduction to 75% of the XELODA starting dose is recommended. In patients with mild renal impairment (creatinine clearance 51-80 mL/min) no adjustment in starting dose is recommended.
  • In phase I studies, those with any abnormal renal function, since toxicity will likely be affected by the presence of any significant renal dysfunction.
  • Cockcroft and Gault Equation:
  • (140 - age [yrs]) (body wt [kg])
  • Creatinine clearance for males = ——————————————
  • (72) (serum creatinine [mg/dL])
  • Creatinine clearance for females = 0.85 x male value

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02297230


Locations
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United States, New York
Weill Medical College of Cornell University
New York, New York, United States, 10065
Sponsors and Collaborators
NYU Langone Health
Investigators
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Principal Investigator: Silvia C Formenti, M.D. Weill Medical College of Cornell University

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Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT02297230     History of Changes
Other Study ID Numbers: 10289
First Posted: November 21, 2014    Key Record Dates
Results First Posted: January 18, 2018
Last Update Posted: October 15, 2018
Last Verified: September 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by NYU Langone Health:
Locally Advanced Breast Cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Capecitabine
Trastuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antineoplastic Agents, Immunological